Polymorphisms in the Platelet‐Endothelial Cell Adhesion Molecule‐1 (PECAM‐1) Gene, Asn563Ser and Gly670Arg, Associated with Myocardial Infarction in the Japanese

Abstract

We examined three missense polymorphisms of platelet‐endothelial cell adhesion molecule‐1 (PECAM‐1), Val125Leu, Asn563Ser, and Gly670Arg, in 136 Japanese patients with myocardial infarction and 235 healthy Japanese controls. We found that these polymorphisms were in linkage disequilibrium with each other and that frequencies of 125Leu, 563Ser, and 670Arg alleles were significantly increased in patients compared with controls (0.522 vs 0.447, p= 0.048; 0.585 vs 0.502, p= 0.030; and 0.577 vs 0.492, p= 0.032, respectively). The frequencies of homozygotes for 563Ser and 670Arg alleles were also significantly increased in the patients (33.1% vs 23.4%, odds risk [OR] = 1.62, p= 0.040, 95% confidence interval [95%CI] = 1.01‐2.58; and 32.4% vs 23.0%, OR = 1.60, p= 0.048, 95%CI = 1.00‐2.57, respectively). These observations suggest that the 563Ser/Ser genotype and 670Arg/Arg genotype of PECAM‐1 are novel genetic risk factors of myocardial infarction in Japanese. Stratification analysis of the patients showed that the associations of these PECAM‐1 genotypes with myocardial infarction were preferentially found in male and younger patients (age of onset of myocardial infarction less than 60 years). In addition, the associations were stronger in patients with three‐vessel disease than in the others and appeared independent of conventional risk factors including smoking, hypertension, diabetes mellitus, hyperlipidemia, and obesity.

Leucine125Valine (Leu125Val) Gene Polymorphism of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) and Myocardial Infarction in Indian Population

“…However 125Leu variant suggested to modulate platelet activation leading to increased risk of MI [18] was more associated with MI patients (0.57) as compared to controls (0.504). Similar finding is also reported by Sasaoka et al [14] in MI. In our study there was significant increase in sPECAM-1 levels in MI patients at acute event (MI-Group-1) as compared to treated patients (MI-Group-2).…”

“…Against these reports Gardemann et al [11] in German population and Elrayees et al [12] in British population did not find Leu125Val gene polymorphism of PECAM-1 as an independent risk factor of CAD. A study by Listi et al [13] in population from Sicily (Italy), reported no significant association of this polymorphism with MI while Sasaoka et al [14] in Japanese population have reported increased 125Leu allele frequency (0.52 vs. 0.447, P = 0.048) in MI patients as compared to controls.…”

“…PECAM-1 is a 130-kDa trans-membrane glycoprotein. It has 6 Ig-like extracellular domains (encoded by exon 3-8) a short trans-membrane domain (encoded by exon 9) and a short cytoplasmic tail (encoded by exon [10][11][12][13][14][15][16] [6,7]. The importance of the first domain of PECAM-1 (encoded by exon 3) is underscored since PECAM-1 forms homophilic binding via its 1st or 1st plus 2nd extracellular Ig-like domains or heterophilic binding with other molecules to mediate cell-cell adhesion [3,8].…”

“…Association between Leu125Val PECAM-1 polymorphism and CAD have been analysed in Caucasians [10][11][12][13], Japanese [14], Chinese [15,16] and Asian Indian residents of Singapore [17]. Although studies discussed so far seem to suggest conflicting data, those investigating the association of PECAM-1 polymorphism and risk of atherogenesis always show increased risk with 125Val [10,[15][16][17] and association of PECAM-1 polymorphism and risk of MI show increased risk with 125Leu [14].…”

“…Although studies discussed so far seem to suggest conflicting data, those investigating the association of PECAM-1 polymorphism and risk of atherogenesis always show increased risk with 125Val [10,[15][16][17] and association of PECAM-1 polymorphism and risk of MI show increased risk with 125Leu [14]. This is thought to be due to different effects of polymorphisms in PECAM-1.…”